We propose to continue our research in the area of acyclic diastereoselective synthesis, with emphasis on novel allylmetalation reactions and fragment assembly aldol reactions which will be developed in the context of the total synthesis of structurally complex, biologically active natural products. Specific goals for the next grant period are: (1)Completion of a Total Synthesis of Tedanolide. The key step of the proposed synthesis was successfully modeled in the previous grant period, thus defining the strategy that will be pursued for completion of the total synthesis. (2) Allylation of Oxonium Ions; Synthesis of the Pyran Nucleus of Scytophycin C. A new strategy for the synthesis of the 2,6-trans dihydropyran unit of scytophycin C will be developed based on the reactions of allylsilanes and oxonium ions followed by ring closing metathesis. (3) Completion of a Total Synthesis of Scytophycin C. The total synthesis of scytophycin C will be completed. The key fragment assembly aldol step was successfully modeled in the previous grant period. (4) Total Synthesis of Spongistatin 1. A synthesis of the E-F bis-pyran unit was completed in the preceding grant period. Studies in the coming grant period will focus on the bifunctional gamma-silylallylborane for the convergent coupling of two aldehydes to generate l,5-anti-pent-2(E)-1,5- diols, which will serve as precursors to the A-B and C-D spiroketals. A strategy for the stereocontrolled synthesis of the C-D spiroketal via inversion of the C(l9) stereocenter also will be developed. (5) Total Synthesis of Apoptolidin. Fragment assembly aldol reactions of alpha- alkoxy ketones will be developed for the synthesis of the C(12)-C(28) segment of apoptolidin. (6) Total Synthesis of Amphidinol 3. Bifunctional allylboranes will be developed for the convergent coupling of two aldehydes to generate l ,5-syn-pent-2(Z)- l ,5-diols, which will serve as key intermediates for the synthesis of the tetrahydropyran units of amphidinol 3. This methodology also provides an alternative strategy for synthesis of the scytophycin C dihydropyran nucleus.